There is strong evidence of an association between maternal smoking during pregnancy and restriction of intrauterine growth, but the effects of this exposure on postnatal linear growth are not well defined. Furthermore, few studies have investigated the role of tobacco smoke exposure also after pregnancy on linear growth until adolescence. In this study we investigated the effect of maternal smoking exposure during pregnancy and preschool age on linear growth from birth to adolescence.

Methods

We evaluated a cohort of children born between 1994 and 1999 in Cuiabá, Brazil, who attended primary health clinics for vaccination between the years 1999 and 2000 (at preschool age) and followed-up after approximately ten years. Individuals were located in public and private schools throughout the country using the national school census. Height/length was measured, and length at birth was collected at maternity departments. Stature in childhood and adolescence was assessed using the height-for-age index sex-specific expressed as z-score from curves published by the World Health Organization. Linear mixed effects models were used to estimate the association between exposure to maternal smoking, during pregnancy and preschool age, and height of children assessed at birth, preschool and school age, adjusted for age of the children.

Results

We evaluated 2405 children in 1999–2000, length at birth was obtained from 2394 (99.5%), and 1716 at follow-up (71.4% of baseline), 50.7% of the adolescents were male. The z-score of height-for-age was lower among adolescents exposed to maternal smoking both during pregnancy and childhood (p

Conclusion

Exposure to maternal smoking not only during pregnancy, but also at early childhood, showed long-term negative effect on height of children until adolescence.

To explore associations of maternal prenatal smoking and child psychological problems and determine the role of causal intrauterine mechanisms.

Patients and Methods

Maternal smoking and child psychological problems were explored in 2 birth cohorts in Pelotas, Brazil (n=509; random sub-sample) and Avon Longitudinal Study of Parents and Children (ALSPAC), Britain (n=6,735). Four approaches for exploring causal mechanisms were applied: 1) cross-population comparisons between a high-income and a middle-income country, 2) multiple adjustment for socioeconomic and parental psychological factors, 3) maternal-paternal comparisons as a test of putative intrauterine effects; and 4) search for specific effects on different behavioural subscales.

Results

Socioeconomic patterning of maternal prenatal smoking was stronger in the ALSPAC compared with the Pelotas cohort. Despite this difference in a key confounder, consistency in observed associations was found between these cohorts. In both cohorts, unadjusted, maternal smoking was associated with greater offspring hyperactivity, conduct/externalizing problems, and peer problems, but not with emotional/internalizing problems. After adjusting for confounders and paternal prenatal smoking, only the association with conduct/externalizing problems persisted in both cohorts (conduct problems in the ALSPAC cohort, odds ratio OR: 1.24 [95% confidence interval (CI): 1.07–1.46], p= .005; externalizing problems in the Pelotas cohort, OR:1.82 [95% CI:1.19–2.78], p=.005; ORs reflect ordinal ORs of maternal smokers having offspring with higher scores). Maternal smoking associations were stronger than paternal smoking associations, although statistical evidence for differences was weak in 1 cohort.

Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach.

Methods and Findings

We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 × 10−9), birth weight (p = 2.19 × 10−15), and gestational age (p = 1.51 × 10−7). Our parental-specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal height resulting in ~0.4 more gestational d. Limitations of this study include potential influences in causal inference by biological pleiotropy, assortative mating, and the nonrandom sampling of study subjects.

Conclusions

Our results demonstrate that the observed association between maternal height and fetal growth measures (i.e., birth length and birth weight) is mainly defined by fetal genetics. In contrast, the association between maternal height and gestational age is more likely to be causal. In addition, our approach that utilizes the genetic score derived from the nontransmitted maternal haplotype as a genetic instrument is a novel extension to the Mendelian randomization methodology in casual inference between parental phenotype (or exposure) and outcomes in offspring.

Using a Mendelian randomization approach, Ge Zhang and colleagues examine the causal relationship between maternal height, birth size, and gestational age at birth.

Editors' Summary

Background

Soon after the birth of a baby, doting parents send messages to friends and relatives or post information on social media sites to let everyone know when their new baby boy or girl was born. They may also post information about how heavy he/she was at birth and his/her length. These pregnancy outcomes, together with gestational age at birth (the length of time that a baby has spent developing in its mother’s womb), affect the baby’s immediate health and survival. Importantly, however, these pregnancy outcomes are also associated with the risk of long-term adverse health outcomes such as obesity, cardiometabolic disorders (heart disease and conditions such as diabetes that affect how the body makes energy from food), and neuropsychiatric conditions (mental disorders attributable to diseases of the nervous system, such as depression). For example, some studies have shown an association between low birth weight and an increased risk of type 2 diabetes later in life.

Why Was This Study Done?

Identification of the environmental and genetic factors that causally influence gestational age, length, and weight at birth would improve our understanding of why these pregnancy outcomes are associated with disease during adulthood and could help in the design of strategies to prevent these diseases. Epidemiological studies (investigations that examine disease patterns in populations) suggest that, compared to tall mothers, short mothers tend to deliver their babies at earlier gestational ages, with lower birth weights and lengths. Epidemiological studies cannot show, however, whether variations in maternal height cause variations in pregnancy outcomes. Other characteristics shared by tall mothers might actually determine the size and gestational age of their offspring (confounding). Here, the researchers use “Mendelian randomization” to assess the causal effect of maternal height on the size and gestational age at birth of babies. Because gene variants are inherited randomly, they are not prone to confounding. So, if maternal height actually affects gestational age and size at birth, genetic variants (instruments) that affect maternal height should be associated with differences in gestational age and size at birth, provided confounding due to the transmission of parental alleles (variant forms of genes; people have two alleles of every gene, one inherited from each parent) is avoided by adjusting for the baby’s genotype.

What Did the Researchers Do and Find?

The researchers used phenotype data (observable characteristics such as maternal height and birth weight of the baby) and single nucleotide polymorphism (SNP; a type of genetic variant) data obtained from 3,486 Nordic mother/baby pairs. Analysis of the phenotype data indicated that maternal height was significantly associated with length, weight, and gestational age at birth (a significant association is unlikely to have arisen by chance). For their Mendelian randomization analysis, the researchers constructed a genetic score based on 697 SNPs known to be associated with adult height. To avoid confounding due to genetic sharing between the mother and baby, they determined which of the height-associated alleles each baby had inherited from its mother and used the nontransmitted haplotype score as a genetic instrument for maternal height (a haplotype is a set of DNA variations that are inherited together). Birth length and weight were significantly associated with both the maternal and paternal transmitted haplotype scores but not with the maternal nontransmitted haplotype score. However, gestational age was significantly but modestly associated with the maternal nontransmitted haplotype score.

What Do These Findings Mean?

The validity of the assumptions that underlie the Mendelian randomization approach and the design of the studies supplying the data for this analysis may affect the accuracy of the findings reported here. Nevertheless, these findings suggest that the observed association between maternal height and fetal growth measurements is mainly determined by the genetics of the baby. That is, differences in maternal height do not cause differences in birth weight or length. Rather, some of the gene variants that the baby inherits from its mother determine both its size and its mother’s height. These findings also provide weak evidence that the association between maternal height and gestational age is causal. Maternal height might, for example, causally influence gestational age by limiting the space available for the baby’s growth before birth. Finally, these findings introduce an extension to the Mendelian randomization approach that can be used to investigate causal associations between parental characteristics and offspring outcomes.

Additional Information

This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001865.

The March of Dimes, a not-for-profit organization for pregnancy and baby health, provides information about low birth weight and its consequences

Nemours, a not-for-profit organization for child health, provides information about the weight of newborn babies (in English and Spanish)

Wikipedia has pages on birth weight, gestational age, and Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)

MedlinePlus provides information and links to additional resources about birth weight and a brief explanation of gestational age (in English and Spanish)

The developmental overnutrition hypothesis suggests that greater maternal obesity during pregnancy results in increased offspring adiposity in later life. If true, this would result in the obesity epidemic progressing across generations irrespective of environmental or genetic changes. It is therefore important to robustly test this hypothesis.

Methods and Findings

We explored this hypothesis by comparing the associations of maternal and paternal pre-pregnancy body mass index (BMI) with offspring dual energy X-ray absorptiometry (DXA)–determined fat mass measured at 9 to 11 y (4,091 parent–offspring trios) and by using maternal FTO genotype, controlling for offspring FTO genotype, as an instrument for maternal adiposity. Both maternal and paternal BMI were positively associated with offspring fat mass, but the maternal association effect size was larger than that in the paternal association in all models: mean difference in offspring sex- and age-standardised fat mass z-score per 1 standard deviation BMI 0.24 (95% confidence interval [CI]: 0.22 to 0.26) for maternal BMI versus 0.13 (95% CI: 0.11, 0.15) for paternal BMI; p-value for difference in effect < 0.001. The stronger maternal association was robust to sensitivity analyses assuming levels of non-paternity up to 20%. When maternal FTO, controlling for offspring FTO, was used as an instrument for the effect of maternal adiposity, the mean difference in offspring fat mass z-score per 1 standard deviation maternal BMI was −0.08 (95% CI: −0.56 to 0.41), with no strong statistical evidence that this differed from the observational ordinary least squares analyses (p = 0.17).

Conclusions

Neither our parental comparisons nor the use of FTO genotype as an instrumental variable, suggest that greater maternal BMI during offspring development has a marked effect on offspring fat mass at age 9–11 y. Developmental overnutrition related to greater maternal BMI is unlikely to have driven the recent obesity epidemic.

Using parental-offspring associations and theFTO gene as an instrumental variable for maternal adiposity, Debbie Lawlor and colleagues found that greater maternal BMI during offspring development does not appear to have a marked effect on offspring fat mass at age 9-11.

Editors' Summary

Background.

Since the 1970s, the proportion of children and adults who are overweight or obese (people who have an unhealthy amount of body fat) has increased sharply in many countries. In the US, 1 in 3 adults is now obese; in the mid-1970s it was only 1 in 7. Similarly, the proportion of overweight children has risen from 1 in 20 to 1 in 5. An adult is considered to be overweight if their body mass index (BMI)—their weight in kilograms divided by their height in meters squared—is between 25 and 30, and obese if it is more than 30. For children, the healthy BMI depends on their age and gender. Compared to people with a healthy weight (a BMI between 18.5 and 25), overweight or obese individuals have an increased lifetime risk of developing diabetes and other adverse health conditions, sometimes becoming ill while they are still young. People become unhealthily fat when they consume food and drink that contains more energy than they need for their daily activities. It should, therefore, be possible to avoid becoming obese by having a healthy diet and exercising regularly.

Why Was This Study Done?

Some researchers think that “developmental overnutrition” may have caused the recent increase in waistline measurements. In other words, if a mother is overweight during pregnancy, high sugar and fat levels in her body might permanently affect her growing baby's appetite control and metabolism, and so her offspring might be at risk of becoming obese in later life. If this hypothesis is true, each generation will tend to be fatter than the previous one and it will be very hard to halt the obesity epidemic simply by encouraging people to eat less and exercise more. In this study, the researchers have used two approaches to test the developmental overnutrition hypothesis. First, they have asked whether offspring fat mass is more strongly related to maternal BMI than to paternal BMI; it should be if the hypothesis is true. Second, they have asked whether a genetic indicator of maternal fatness—the “A” variant of the FTO gene—is related to offspring fat mass. A statistical association between maternal FTO genotype (genetic make-up) and offspring fat mass would support the developmental nutrition hypothesis.

What Did the Researchers Do and Find?

In 1991–1992, the Avon Longitudinal Study of Parents and Children (ALSPAC) enrolled about 14,000 pregnant women and now examines their offspring at regular intervals. The researchers first used statistical methods to look for associations between the self-reported prepregnancy BMI of the parents of about 4,000 children and the children's fat mass at ages 9–11 years measured using a technique called dual energy X-ray absorptiometry. Both maternal and paternal BMI were positively associated with offspring fat mass (that is, fatter parents had fatter children) but the effect of maternal BMI was greater than the effect of paternal BMI. When the researchers examined maternal FTO genotypes and offspring fat mass (after allowing for the offspring's FTO genotype, which would directly affect their fat mass), there was no statistical evidence to suggest that differences in offspring fat mass were related to the maternal FTO genotype.

What Do These Findings Mean?

Although the findings from first approach provide some support for the development overnutrition hypothesis, the effect of maternal BMI on offspring fat mass is too weak to explain the recent obesity epidemic. Developmental overnutrition could, however, be responsible for the much slower increase in obesity that began a century ago. The findings from the second approach provide no support for the developmental overnutrition hypothesis, although these results have wide error margins and need confirming in a larger study. The researchers also note that the effects of developmental overnutrition on offspring fat mass, although weak at age 9–11, might become more important at later ages. Nevertheless, for now, it seems unlikely that developmental overnutrition has been a major driver of the recent obesity epidemic. Interventions that aim to improve people's diet and to increase their physical activity levels could therefore slow or even halt the epidemic.

Additional Information.

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050033.

See a related PLoS Medicine Perspective article

The MedlinePlus encyclopedia has a page on obesity (in English and Spanish)

The US Centers for Disease Control and Prevention provides information on all aspects of obesity (in English and Spanish)

Socio-economic inequalities in attained height have been reported in many countries. The aim of this study was to explore the age at which maternal education inequalities in child height emerge among children from a middle-income country. Using data from the 2004 Pelotas cohort study from Brazil we modelled individual height growth trajectories in 2106 boys and 1947 girls from birth to 4 years using a linear spline mixed-effects model. We examined the associations of maternal education with birth length and trajectories of growth in length/height, and explored the effect of adjusting for a number of potential confounder or mediator factors.

We showed linear and positive associations of maternal education with birth length and length/height growth rates at 0–3 months and 12–29/32 months with very little association at 3–12 months, particularly in boys. By age 4 years the mean height of boys was 101.06 cm (SE = 0.28) in the lowest and 104.20 cm (SE = 0.15) in the highest education category (mean difference 3.14 cm, SE = 0.32, P < 0.001). Among girls the mean height was 100.02 cm (SE = 0.27) and 103.03 cm (SE = 0.15) in the lowest and highest education categories, respectively (mean difference 3.01 cm, SE = 0.31, P < 0.001). For both boys and girls there was on average a 3-cm difference between the extreme education categories. Adjusting for maternal height reduced the observed birth length differences across maternal education categories, but differences in postnatal growth rates persisted.

Our data demonstrate an increase in the absolute and relative inequality in height after birth; inequality increases from approximately 0.2 standard deviations of birth length to approximately 0.7 standard deviations of height at age 4, indicating that height inequality, which was already present at birth, widened through differential growth rates to age 2 years.

To evaluate the effect of (1) maternal smoking during pregnancy; and (2) partner smoking on offspring's height in infancy, childhood, and adolescence.

Methods

All hospital live births from 1993 (5,249) were identified, and these infants were followed up at several ages. Height for age, expressed as z-scores using the World Health Organization growth curves, was measured at all follow-up visits. Maternal smoking during pregnancy was collected retrospectively at birth and analyzed as number of cigarettes/day smoked categorized in four categories (never smoked, <10, 10–19, and ≥20 cigarettes/day). Partner smoking was analyzed as a dichotomous variable (No/Yes). Unadjusted and adjusted analyses were performed by use of linear regression.

Results

The prevalence of self-reported maternal smoking during pregnancy was 33.5%. In the crude analysis, the number of cigarettes/day smoked by the mother during pregnancy negatively affected offspring's height in infancy, childhood, and adolescence. After adjustment for confounders and mediators, this association remained statistically significant, although the magnitude of the regression coefficients was reduced. Paternal smoking was not associated with offspring's height in the adjusted analyses.

Conclusions

In addition to the well-known harmful effects of smoking, maternal smoking during pregnancy negatively affects offspring's height. Public health policies aimed at continuing to reduce the prevalence of maternal smoking during pregnancy must be encouraged.

Childhood intelligence is an important determinant of health outcomes in adulthood. The first years of life are critical to child development. This study aimed to identify early life (perinatal and during the first year of life) predictors of low cognitive performance at age 6.

Methods

A birth cohort study started in the city of Pelotas, southern Brazil, in 2004 and children were followed from birth to age six. Information on a broad set of biological and social predictors was collected. Cognitive ability—the study outcome—was assessed using the Wechsler Intelligence Scale for Children (WISC). IQ scores were standardized into z-scores and low IQ defined as z

Results

The proportion of children with IQ z-score

Conclusions

The study results suggest that a child’s and her/his family’s social conditions are strong predictors of cognitive ability in childhood. Interventions for promoting a healthy early childhood development are needed targeting children at risk of low IQ so that they can reach their full cognitive potential.

Electronic supplementary material

The online version of this article (doi:10.1186/s12887-014-0308-1) contains supplementary material, which is available to authorized users.

Background Maternal smoking during pregnancy is associated with reduced offspring birth length and has been postulated as a risk factor for obesity. Causality for obesity is not established. Causality is well-supported for birth length, but evidence on persistence of height deficits is inconsistent.

Methods We examined the association between maternal smoking during pregnancy and trajectories of offspring height (0–10 years, N = 9424), ponderal index (PI) (0–2 years, N = 9321) and body mass index (BMI) (2–10 years, N = 8887) in the Avon Longitudinal Study of Parents and Children. To strengthen inference, measured confounders were controlled for, maternal and partner smoking associations were compared, dose–response and associations with post-natal smoking were examined.

Results Maternal smoking during pregnancy was associated with shorter birth length, faster height growth in infancy and slower growth in later childhood. By 10 years, daughters of women who smoke during pregnancy are on average 1.11 cm (SE = 0.27) shorter after adjustment for confounders and partner smoking; the difference is 0.22 cm (SE = 0.22) for partner's smoking. Maternal smoking was associated with lower PI at birth, faster PI increase in infancy, but not with BMI changes 2–10 years. Associations were stronger for maternal than partner smoking for PI at birth and PI changes in infancy, but not for BMI changes after 2 years. A similar dose–response in both maternal and partner smoking was seen for BMI change 2–10 years.

Conclusion Maternal smoking during pregnancy has an intrauterine effect on birth length, and possibly on adiposity at birth and changes in height and adiposity in infancy. We do not find evidence of a specific intrauterine effect on height or adiposity changes after the age of 2 years.

We examined the associations between socioeconomic trajectories from birth to adulthood and gestational age and birth size in the next generation, using linked data from two population-based birth cohorts carried out in a Brazilian city. By comparing socioeconomic trajectories of mothers and fathers, we attempted to identify-specific effects of maternal and paternal socioeconomic trajectory on offspring birth weight, birth length, head circumference and gestational age at birth.

Methods

2 population-based birth cohort studies were carried out in 1982 and 2004 in Pelotas (Brazil); 156 mothers and 110 fathers from the earlier cohort had children in 2004. Gestational age and birth length, weight and head circumference were measured. Analyses were carried out separately for mothers and fathers. Mediation analyses assessed the role of birth weight and adult body mass index (BMI).

Results

Among mothers, but not for fathers, childhood poverty was strongly associated with smaller size in the next generation (about 400 g in weight and 1.5 cm in height) and shorter gestations (about 2 weeks). Adult poverty did not play a role. For mothers, the associations with gestational age, birth length and weight—but not with head circumference—persisted after adjusting for maternal birth weight and for the height and weight of the grandmother. Maternal birth weight did not mediate the observed associations, but high maternal BMI in adulthood was partly responsible for the association with gestational age.

Conclusions

Strong effects of early poverty on gestational age and birth size in the next generation were observed among mothers, but not among fathers. These findings suggest a specific maternal effect of socioeconomic trajectory, and in particular of early poverty on offspring size and duration of pregnancy.

To examine the association of maternal and/or paternal smoking during pregnancy with offspring cardio-metabolic risk (CMR) factors at adolescence and early adulthood, taking into account socio-demographic, medical and lifestyle characteristics of parents and offspring, as well as offspring common genetic variation.

Methods

We used a population-based cohort of all 17 003 births in Jerusalem during 1974–76, with available archival data on parental and birth characteristics. Measurements at age 17 were assessed at military induction examinations for 11 530 offspring. 1440 offspring from the original 1974–1976 birth cohort were sampled using a stratified sampling approach, and were interviewed and examined at age 32. Parental smoking during pregnancy (i.e. maternal, paternal and any parent) was primarily defined dichotomously (any number of cigarettes smoked daily by mother or father during pregnancy vs. non-smokers). Additionally, smoking was assessed by quantity of cigarettes smoked daily. Linear regression models were used to evaluate the associations of parental smoking during pregnancy with various offspring CMR factors, after controlling for potential confounders and for genetic variation in candidate genes.

Results

Prevalence of exposure to parental smoking in-utero (i.e. smoking of any parent) was 53.2% and 48.4% among the 17 years old and 32 years old samples, respectively. At age 17, smoking of at least one parent during pregnancy was significantly associated with weight (B=1.39), height (B=0.59), BMI (B=0.32) and pulse rate (B=−0.78) (p-values<0.001). At age 32, parental smoking, adjusted for covariates, was associated with 2.22 kg higher mean offspring weight, 0.95 cm higher mean offspring height, 0.57 kg/m2 higher BMI, and 1.46 cm higher waist-circumference (p-values≤0.02). Similar results, reflecting a dose response, were observed when maternal and paternal smoking were assessed by number of cigarettes smoked daily.

Conclusions

This prospective study demonstrates a potential long-term adverse effect of parental smoking during pregnancy on offspring health and calls for increasing efforts to promote smoking cessation of both parents before pregnancy.

We investigated an intrauterine influence of maternal smoking during pregnancy on childhood bone mass. Daughters, but not sons, of mothers who smoked had higher bone mass at age 10 years. This appears to be due to familial factors related to parental smoking influencing increased offspring adiposity rather than a direct intrauterine effect.

Introduction

Neonatal studies have demonstrated an adverse relationship between maternal smoking in pregnancy and foetal bone mineral accrual. We aimed to investigate an intrauterine influence of maternal smoking during pregnancy on offspring bone mass at mean age 9.9 years.

Methods

We compared associations of maternal and paternal smoking in pregnancy with offspring total body less head (TBLH) and spine bone mineral content (BMC), bone area (BA), bone mineral density (BMD) and area-adjusted BMC (ABMC) in 7,121 children in the Avon Longitudinal Study of Parents and Children.

Results

Maternal smoking in any trimester was associated with increased TBLH BMC, BA and BMD in girls (mean difference [95% CI] (sex-specific SD scores), 0.13 [0.05–0.22], 0.13 [0.04–0.21], 0.13 [0.04–0.22], respectively) but not boys (0.01 [−0.07–0.09], 0.00 [−0.08–0.08], 0.04 [−0.05–0.12]), and also with spine BMC, BA and BMD in girls (0.13 [0.03–0.23], 0.12 [0.03–0.22], 0.10 [0.00–0.21]) but not boys (0.03 [−0.06–0.12], 0.00 [−0.09–0.09], 0.05 [−0.04–0.14]), but not with ABMC. Paternal smoking associations were similar, with no statistical evidence for a difference between maternal and paternal effects. Maternal associations increased on adjustment for offspring birth weight and gestational age, but attenuated to the null after adjustment for current height and weight.

Conclusions

We found little evidence that maternal smoking was related to bone mass in boys. In girls, maternal smoking associations were similar to those of paternal smoking, suggesting that these were attributable to shared familial characteristics, not intrauterine mechanisms.

Electronic supplementary material

The online version of this article (doi:10.1007/s00198-010-1415-y) contains supplementary material, which is available to authorized users.

We investigated the association between maternal anthropometric measurements in prepregnancy and at the end of pregnancy and their children's systolic (SBP) and diastolic (DBP) blood pressure at 11 years of age, in a prospective cohort study.

Methods

All hospital births which took place in 1993 in the city of Pelotas - Brazil, were identified (5,249 live births). In 2004, the overall proportion of follow-up was 85% and we obtained arterial blood pressure measurements of 4,452 adolescents.

Results

Independent variables analyzed included maternal prepregnancy weight and body mass index (BMI) and maternal weight, and height at the end of pregnancy. Multiple linear regression analysis controlling for the following confounders were carried out: adolescent's skin color, family income at birth, smoking, alcohol intake during pregnancy, and gestational arterial hypertension. Mean SBP and DBP were 101.9 mmHg (SD 12.3) and 63.4 mmHg (SD 9.9), respectively. Maternal prepregnancy weight and BMI, and weight at the end of pregnancy were positively associated with both SBP and DBP in adolescent subjects of both sexes; maternal height was positively associated with SBP only among males.

Conclusions

Adequate evaluation of maternal anthropometric characteristics during pregnancy may prevent high levels of blood pressure among adolescent children.

Background Some studies suggest that weight gain in childhood may increase the risk of chronic diseases in adulthood, and recent studies have noticed that the timing of weight gain may be related to its long-term consequence. However, weight gain in childhood has clear short-term benefits, and the literature on the pro and cons of weight gain in childhood is limited.

Methods In 1982, all 5914 hospital births (over 99% of all deliveries) occurring in Pelotas, Southern Brazil, were identified and studied prospectively on several occasions. In 2004–05, we attempted to trace the whole cohort and information on offspring birthweight was collected. Conditional growth modelling was used to assess the association between offspring birthweight and weight gain from birth to 20 months, and from 20 to 42 months.

Results In 2004–05, we interviewed 4297 subjects, with a follow-up rate of 77.4%. This manuscript includes data from 848 women who had already delivered a child and 525 men who were fathers at the mean age of 23 years. Maternal birthweight, weight and length for age Z-score at 20 months of age were positively associated with next-generation birthweight, whereas paternal variables were not related to the outcome. Conditional growth modelling analyses showed that women whose weight gain in the first 20 months of life was faster than predicted had heavier babies, whereas paternal weight gain was not associated. The association was strongest for mothers whose birthweight for gestational age was in the lowest tertile.

Conclusion Maternal, but not paternal birthweight and weight gain in early childhood are positively associated with next-generation birthweight.

There is a demand for strategies to promote smoking cessation in high-risk populations like smoking pregnant women and their partners. The objectives of this study were to investigate parental smoking behaviour during pregnancy after introduction of a prenatal, structured, multi-disciplinary smoking cessation programme in primary care, and to compare smoking behaviour among pregnant women in the city of Trondheim with Bergen and Norway.

Methods

Sequential birth cohorts were established to evaluate the intervention programme from September 2000 to December 2004 in primary care as a part of the Prevention of Allergy among Children in Trondheim study (PACT). The primary outcome variables were self reported smoking behaviour at inclusion and six weeks postnatal. Data from the Medical Birth Registry of Norway (MBR) were used to describe smoking cessation during pregnancy in Trondheim, Bergen and Norway 1999–2004.

Results

Maternal smoking prevalence at inclusion during pregnancy were 5% (CI 95% 4–6) in the intervention cohort compared to 7% (CI 95% 6–9), p = 0.03, in the control cohort. Of the pre-pregnancy maternal smokers 25% (CI 95% 20–31) and 32% (CI 95% 26–38), p = 0.17, were still smoking at inclusion in the intervention and control cohorts, respectively. Six weeks postnatal 72% (CI 95% 59–83) and 68% (CI 95% 57–77), p = 0.34 of the maternal smokers at inclusion still smoked. No significant difference in paternal smoking between the cohorts was found after the intervention period. Data from the MBR showed a significantly higher proportion of women who stopped smoking during pregnancy in Trondheim than in Bergen in 2003 and 2004, p = 0.03 and < 0.001, respectively.

Conclusion

No impact on parental smoking behaviour between the cohorts was observed after the smoking intervention programme. Of the women who stopped smoking during pregnancy most of them stopped smoking before the intervention. However, we observed a significantly higher quitting rate in Trondheim than in Bergen in 2003 and 2004 which may have been facilitated by the supplemental attention on smoking behaviour the PACT study initiated.

Maternal smoking during pregnancy is associated with short-term and also long-term harmful effects on offspring.

Objective

The aim of this study is to evaluate the associations of maternal smoking during pregnancy with offspring bone health at 18 years old, and the role of birth weight and contemporaneous height, weight and body mass index (BMI) in this association.

Data from the 1993 Pelotas Birth Cohort were analyzed using path analysis stratified by sex.

Each additional cigarette smoked during pregnancy was associated with a lower BMC by − 4.20 g in males (95% CI − 8.37; − 0.05), but not in females [− 2.22 g (95% CI − 5.49; 1.04)]; weaker inverse associations were observed for BMD. This inverse association was explained by the influence of maternal smoking on birth weight and contemporaneous anthropometry, particularly height. A 1 kg higher birth weight was associated with a higher BMC by around 144 g in males and by around 186 g in females, and also with a higher BMD by around 0.019 g/cm2 in males and by around 0.018 g/cm2 in females, respectively.

Conclusions

Lifecourse analysis using path models has enabled to evaluate the role of mediators in the associations of maternal smoking during pregnancy and birth weight with bone mass in the offspring, thus generating improved understanding of the etiology of bone health and the importance of early life experiences.

Highlights

•Each additional cigarette smoked during pregnancy was associated with a lower BMC by − 4.20 g in males at 18 years old.•This inverse association was mediated by birth weight and contemporaneous anthropometry, particularly height.•Birth weight was associated with a higher BMD/BMC in both sexes.

Socioeconomic inequalities in health outcomes are dynamic and vary over time. Differences between countries can provide useful insights into the causes of health inequalities. The study aims to compare the associations between two measures of socioeconomic position (SEP)—maternal education and family income—and maternal and infant health outcomes between ALSPAC and Pelotas cohorts.

Methods

Birth cohort studies were started in Avon, UK, in 1991 (ALSPAC) and in the city of Pelotas, Brazil, in 1982, 1993 and 2004. Maternal outcomes included smoking during pregnancy, caesarean section and delivery not attended by a doctor. Infant outcomes were preterm birth, intra-uterine growth restriction (IUGR) and breast feeding for <3 months. The relative index of inequality was used for each measure of SEP so that results were comparable between cohorts.

Results

An inverse association (higher prevalence among the poorest and less educated) was observed for almost all outcomes, with the exception of caesarean sections where a positive association was found. Stronger income-related inequalities for smoking and education-related inequalities for breast feeding were found in the ALSPAC study. However, greater inequalities in caesarean section and education-related inequalities in preterm birth were observed in the Pelotas cohorts.

Conclusions

Mothers and infants have more adverse health outcomes if they are from poorer and less well-educated socioeconomic backgrounds in both Brazil and the UK. However, our findings demonstrate the dynamic nature of the association between SEP and health outcomes. Examining differential socioeconomic patterning of maternal and infant health outcomes might help understanding of mechanisms underlying such inequalities.

Maternal smoking during pregnancy is a major cause of intrauterine growth restriction and childhood obesity, but only a few studies have examined the association of smoking cessation before and during pregnancy with fetal and childhood growth. We examined this association in a prospective cohort study in Japan.

Methods

Our study included children born between 1991 and 2006 and their mothers. Using a questionnaire, maternal smoking status was recorded at pregnancy. The anthropometric data of the children were collected during a medical check-up at age 3 years. Multiple linear and logistic regression models were used for data analysis stratified by sex.

Results

In total, 2663 mothers reported their smoking status during early pregnancy, and data were collected from 2230 (83.7%) children at age 3 years. Maternal smoking during pregnancy was associated with a significant reduction in birth weight (approximately 120–150 g). Body mass index at age 3 years was significantly higher among boys born to smoking mothers than among boys born to nonsmoking mothers. Maternal smoking during pregnancy was associated with overweight at age 3 years among boys (adjusted odds ratio, 2.4; 95% CI, 1.03–5.4). However, among women who stopped smoking in early pregnancy, there was no increase in the risks of a small for gestational age birth or childhood overweight at age 3 years.

Conclusions

Children born to mothers who stopped smoking before or during early pregnancy had appropriate fetal and childhood growth.

Advancing maternal age has been related to increased risk of fetal death and morbidity, as well as higher fracture risk during childhood, in the offspring. In the present study, we demonstrate that advancing maternal age is independently associated with reduced bone mass in the young adult male offspring.

Introduction

In Sweden the maternal age in both primi- and multipara mothers has steadily increased during the last three decades. It has been previously reported that advancing maternal age increases the risk of fetal death, but also of morbidity in the offspring, such as chromosome abnormalities, leukemia, diabetes mellitus type 1, and schizophrenia. Whether or not maternal age influences peak bone mass has not been reported. The aim of the present study was to investigate whether a high maternal age was associated with lower peak bone mass, as measured using DXA in a large cohort of male offspring [the Gothenburg Osteoporosis and Obesity Determinants study (GOOD)].

Methods

Through the Swedish multi-generation register, we identified the mothers of 1,009 GOOD study subjects. From the Swedish medical birth register detailed information about the medical circumstances at the time of child birth were obtained, including maternal and offspring anthropometrics (birth height and weight), maternal age, and smoking habits, parity and length of pregnancy.

Results

Maternal age was inversely correlated to areal BMD (aBMD) at the total body (r =−0.07, p = 0.03) and the lumbar spine (r =−0.09, p

Conclusions

In conclusion, our results suggest that advancing maternal age could negatively affect bone mass in young adult men.

In a prospective cohort from Brazil, we evaluated the incidence of fractures from birth to early adolescence and examined risk factors for fractures. The incidence was 14.2% (95%CI 13.2, 15.2). Male sex, birth length, and maternal age at delivery were positively associated with the risk of fractures.

Introduction

This study aims to evaluate the incidence of fractures from birth to 11 years of age and to explore the effect of early life variables on the risk of fractures.

Methods

All children (N = 5,249) born in 1993 in the city of Pelotas, Brazil were enrolled in a prospective birth cohort study. In 2004–2005, 87.5% of the cohort members were sought for a follow-up visit. History of fractures, including anatomic site and age of the fracture were asked to mothers.

Results

The incidence of fractures from birth to 11 years of age was 14.2% (95%CI 13.2, 15.2). Out of the 628 subjects who experienced a fracture, 91 reported two and only 20 reported three or more fractures. Male sex, birth length, and maternal age at delivery were positively associated with the risk of fractures. No consistent associations were found for family income, maternal body mass index, smoking during pregnancy, and birth weight.

Conclusions

Birth length seems to have long-term effect on musculoskeletal health. The higher risk of fractures among children of older mothers needs to be confirmed by other studies. In accordance to the developmental origins of diseases, fractures seem to be, at least in part, programmed in early life.

To identify predictors of postnatal catch-up growth from birth to two years and its relation to size and obesity at five years.

Design

Regional prospective cohort study.

Setting

Avon longitudinal study of pregnancy and childhood, United Kingdom.

Subjects

848 full term singletons from a 10% random sample of the Avon longitudinal study of pregnancy and childhood.

Main outcome measures

Maternal birth weight, prepregnancy weight, pregnancy weight gain, height, smoking, and parity, and paternal height. Weight and length of infants at birth, two years, and five years expressed as standard deviation (SD) scores from the UK reference scores for 1990. Percentage fat mass and total fat mass (estimated from skinfolds) and waist circumference at five years.

Results

Size at birth was representative of the national reference. Overall, 30.7% (260 of 848) of infants showed a gain in SD score for weight greater than 0.67 SD scores between zero and two years, indicating clinically significant catch-up growth. These children had lower weight, length, and ponderal index at birth than other children, and were more often from primiparous pregnancies. They also had taller fathers than other children, and their mothers had lower birth weights and were more likely to smoke during pregnancy. Children who showed catch-up growth between zero and two years were heavier, taller, and fatter (body mass index, percentage body fat, and waist circumference) at five years than other children.

Conclusions

In this contemporary well nourished cohort, catch-up growth was predicted by factors relating to intrauterine restraint of fetal growth. Children who showed catch-up growth between zero and two years were fatter and had more central fat distribution at five years than other children. Mechanisms that signal and regulate early catch-up growth in the postnatal period may influence associations between small size at birth and risks for disease in adulthood.

Martina Persson and colleagues use a Swedish national database to investigate the association between maternal body mass index in early pregnancy and severe asphyxia-related outcomes in infants delivered at term.

Please see later in the article for the Editors' Summary

Background

Maternal overweight and obesity increase risks of pregnancy and delivery complications and neonatal mortality, but the mechanisms are unclear. The objective of the study was to investigate associations between maternal body mass index (BMI) in early pregnancy and severe asphyxia-related outcomes in infants delivered at term (≥37 weeks).

Methods and Findings

A nation-wide Swedish cohort study based on data from the Medical Birth Register included all live singleton term births in Sweden between 1992 and 2010. Logistic regression analyses were used to obtain odds ratios (ORs) with 95% CIs for Apgar scores between 0 and 3 at 5 and 10 minutes, meconium aspiration syndrome, and neonatal seizures, adjusted for maternal height, maternal age, parity, mother's smoking habits, education, country of birth, and year of infant birth. Among 1,764,403 term births, 86% had data on early pregnancy BMI and Apgar scores. There were 1,380 infants who had Apgar score 0–3 at 5 minutes (absolute risk = 0.8 per 1,000) and 894 had Apgar score 0–3 at 10 minutes (absolute risk = 0.5 per 1,000). Compared with infants of mothers with normal BMI (18.5–24.9), the adjusted ORs (95% CI) for Apgar scores 0–3 at 10 minutes were as follows: BMI 25–29.9: 1.32 (1.10–1.58); BMI 30–34.9: 1.57 (1.20–2.07); BMI 35–39.9: 1.80 (1.15–2.82); and BMI ≥40: 3.41 (1.91–6.09). The ORs for Apgar scores 0–3 at 5 minutes, meconium aspiration, and neonatal seizures increased similarly with maternal BMI. A study limitation was lack of data on effects of obstetric interventions and neonatal resuscitation efforts.

Conclusion

Risks of severe asphyxia-related outcomes in term infants increase with maternal overweight and obesity. Given the high prevalence of the exposure and the severity of the outcomes studied, the results are of potential public health relevance and should be confirmed in other populations. Prevention of overweight and obesity in women of reproductive age is important to improve perinatal health.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

Economic, technologic, and lifestyle changes over the past 30 years have created an abundance of cheap, accessible, high-calorie food. Combined with fewer demands for physical activity, this situation has lead to increasing body mass throughout most of the world. Consequently, being overweight or obese is much more common in many high-income and low-and middle-income countries compared to 1980. Worldwide estimates put the percentage of overweight or obese adults as increasing by over 10%, between 1980 and 2008.

As being overweight becomes a global epidemic, its prevalence in women of reproductive age has also increased. Pregnant women who are overweight or obese are a cause for concern because of the possible associated health risks to both the infant and mother. Research is necessary to more clearly define these risks.

Why Was This Study Done?

In this study, the researchers investigated the complications associated with excess maternal weight that could hinder an infant from obtaining enough oxygen during delivery (neonatal asphyxia). All fetuses experience a loss of oxygen during contractions, however, a prolonged loss of oxygen can impact an infant's long-term development. To explore this risk, the researchers relied on a universal scoring system known as the Apgar score. An Apgar score is routinely recorded at one, five, and ten minutes after birth and is calculated from an assessment of heart rate, respiratory effort, and color, along with reflexes and muscle tone. An oxygen deficit during delivery will have an impact on the score. A normal score is in the range of 7–10. Body mass index (BMI) a calculation that uses height and weight, was used to assess the weight status (i.e., normal, overweight, obese) of the mother during pregnancy.

What Did the Researchers Do and Find?

Using the Swedish medical birth registry (a database including nearly all the births occurring in Sweden since 1973) the researchers selected records for single births that took place between 1992 to 2010. The registry also incorporates prenatal care data and researchers further selected for records that included weight and height measurement taken during the first prenatal visit. BMI was calculated using the weight and height measurement. Based on BMI ranges that define weight groups as normal, overweight, and obesity grades I, II, and III, the researchers analyzed and compared the number of low Apgar scoring infants (Apgar 0–3) in each group. Mothers with normal weight gave birth to the majority of infants with Apgar 0–3. In comparison the proportion of low Apgar scores were greater in babies of overweight and obese mothers. The researchers found that the rates of low Apgar scores increased with maternal BMI: the authors found that rates of low Apgar score at 5 minutes increased from 0.4 per 1,000 among infants of underweight women (BMI <18.5) to 2.4 per 1,000 among infants of women with obesity class III (BMI ≥40). Furthermore, overweight (BMI 25.0–29.9) was associated with a 55% increased risk of low Apgar scores at 5 minutes; obesity grade I (BMI 30–34.9) and grade II (BMI 35.0–39.9) with an almost 2-fold and a more than 2-fold increased risk, respectively; and obesity grade ΙΙΙ (BMI ≥40.0) with a more than 3-fold increase in risk. Finally, maternal overweight and obesity also increase the risks for seizures and meconium aspiration in the neonate.

What Do These Findings Mean?

These findings suggest that the risk of experiencing an oxygen deficit increases for the babies of women who are overweight or obese. Given the high prevalence of overweight and obesity in many countries worldwide, these findings are important and suggest that preventing women of reproductive age from becoming overweight or obese is therefore important to the health of their children.

A limitation of this study is the lack of data on the effects of clinical interventions and neonatal resuscitation efforts that may have been performed at the time of birth. Also Apgar scoring is based on five variables and a low score is not the most direct way to determine if the infant has experienced an oxygen deficit. However, these findings suggest that early detection of perinatal asphyxia is particularly relevant among infants of overweight and obese women although more studies are necessary to confirm the results in other populations.

Additional Information

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001648.

The US National Institutes of Health explains and calculates body mass index

The NIH also defines the Apgar scoring system

The United Kingdom's National Health Service has information for pregnant woman who are overweight

The UK-based Overseas Development Institute discusses how changes in diet have led to a worldwide health crisis in its “Future Diets” publication

Information about the Swedish health care system is available

Information in English is available from the National Board of Health and Welfare in Sweden

Shorter stature is associated with greater all cause and heart disease mortality, but taller stature with increased risk of cancer mortality. Though childhood environment is important in determining height, limited data address how maternal depression affects linear growth in children. We examined the relationships between antenatal and postpartum depressive symptoms and child height and linear growth from birth to age 3 years in a U.S. sample.

Methods

Subjects were 872 mother-child pairs in Project Viva, a prospective pre-birth cohort study. The study population is relatively advantaged with high levels of income and education and low risk of food insecurity. We assessed maternal depression at mid-pregnancy (mean 28 weeks' gestation) and 6 months postpartum with the Edinburgh Postnatal Depression Scale (score > = 13 on 0–30 scale indicating probable depression). Child outcomes at age 3 were height-for-age z-score (HAZ) and leg length. HAZ was also available at birth and ages 6 months, 1, 2, and 3 years.

Background: Cigarette smoking has been associated with acute myeloid leukemia (AML) but hypothesis on the association between maternal smoking during pregnancy and childhood leukemia remains unclear. Objectives: To investigate the association between maternal exposure to tobacco smoking during pregnancy and early age (<2 year) leukemia (EAL). Methods: A hospital-based multicenter case-control study aiming to explore EAL risk factors was carried out in Brazil during 1999–2007. Data were collected by direct interview with the biological mothers using a standardized questionnaire. The present study included 675 children (193 acute lymphoid leukemia – ALL, 59 AML and 423 controls), being the latter age frequency matched and paired by area of residence with the cases. Unconditional logistic regression was performed, and odds ratios (OR) on the association between tobacco smoking (3 months before pregnancy, during pregnancy, and 3 months after delivery) and EAL were ascertained after adjustment for selected variables (maternal age at birth and education, birth weight, infant skin color, and oral contraceptives use during pregnancy). Results: Smoking was reported by 17.5% of case mothers and 20.6% of controls. Among women who reported to have smoked 20 or more cigarettes during the index pregnancy, an adjusted OR = 5.28 (95% CI 1.40–19.95) for ALL was observed. Heavy smoking during breastfeeding yielded an adjusted risk estimate for ALL, OR = 7.78 (95% CI 1.33–45.5). No dose-response effect was observed according to smoking exposure during pregnancy and EAL. An association between secondhand smoking during pregnancy or breastfeeding was not observed. Conclusion: An association between maternal smoking and EAL in the offspring was restricted to women who have reported an intense exposure to tobacco smoke during pregnancy and breastfeeding.

This study was aimed at assessing the effect of maternal smoking during pregnancy on metabolic cardiovascular risk factors in early adulthood in a Brazilian birth cohort, after controlling for possible confounding variables and health behaviors in early adulthood.

Methods

In 1982, the maternity hospitals in Pelotas, southern Brazil, were visited and all births were identified. Those livebirths whose family lived in the urban area of the city were studied prospectively. In 2004–2005, we attempted to follow the whole cohort, the subjects were interviewed, examined and blood sample was collected. The following outcomes were studied: blood pressure; HDL cholesterol; triglycerides; random blood glucose and C-reactive protein. To explore the effect of maternal smoking, we adjusted the coefficients for the following possible mediators: perinatal factors (low birthweight and preterm births); adult behavioral factors (physical activity, dietary pattern, intake of fat and fiber, and tobacco smoking) and adult anthropometry (body mass index and waist circumference).

Results

In 2004–2005, we interviewed 4297 subjects, with a follow-up rate of 77.4%. The only significant finding in the unadjusted analyses was lower HDL cholesterol among females. After adjustment for lifestyle variables in early adulthood, birthweight and waist circumference, the difference in HDL levels between offspring of smokers and non-smokers reduced from −2.10 mg/dL (95% confidence interval: −3.39; −0.80) to −1.03 mg/dL (−2.35; 0.30).

Conclusion

Evidence that maternal smoking during pregnancy programs offspring metabolic cardiovascular risk factors are scarce, and reported associations are likely due to postnatal exposure to lifestyle patterns.

Maternal smoking during pregnancy has been found to influence newborn DNA methylation in genes involved in fundamental developmental processes. It is pertinent to understand the degree to which the offspring methylome is sensitive to the intensity and duration of prenatal smoking. An investigation of the persistence of offspring methylation associated with maternal smoking and the relative roles of the intrauterine and postnatal environment is also warranted. In the Avon Longitudinal Study of Parents and Children, we investigated associations between prenatal exposure to maternal smoking and offspring DNA methylation at multiple time points in approximately 800 mother–offspring pairs. In cord blood, methylation at 15 CpG sites in seven gene regions (AHRR, MYO1G, GFI1, CYP1A1, CNTNAP2, KLF13 and ATP9A) was associated with maternal smoking, and a dose-dependent response was observed in relation to smoking duration and intensity. Longitudinal analysis of blood DNA methylation in serial samples at birth, age 7 and 17 years demonstrated that some CpG sites showed reversibility of methylation (GFI1, KLF13 and ATP9A), whereas others showed persistently perturbed patterns (AHRR, MYO1G, CYP1A1 and CNTNAP2). Of those showing persistence, we explored the effect of postnatal smoke exposure and found that the major contribution to altered methylation was attributed to a critical window of in utero exposure. A comparison of paternal and maternal smoking and offspring methylation showed consistently stronger maternal associations, providing further evidence for causal intrauterine mechanisms. These findings emphasize the sensitivity of the methylome to maternal smoking during early development and the long-term impact of such exposure.